Recently, since patients with diabetes mellitus have markedly increased, hemodialysis with the progression of diabetic nephropathy has increased. These patients with renal failure, inhibited renal phosphate excretion, show hyperphosphatemia because serum phosphate cannot be sufficiently removed by hemodialysis. Hyperphosphatemia is a causative factor of secondary hyperparathyroidism and renal osteodystrophy by an excessive secretion of parathyroid hormone, and it also induces ectopic calcification in cardiovascular system by increase and accumulation of calcium phosphate, considering one of the causes of the cardiovascular diseases.
As the anti-hyperphosphatemia agent, various metallic salts (e.g. aluminum preparation, calcium preparation, rare earth metal salts such as Lanthanum Carbonate) and polymer preparation such as Sevelamer Hydrochloride and cholesterol sequestrants have been marketed and researched. However, these drugs have some problems such as large amounts of dosage required, expression of adverse effects such as gastrointestinal disorder, and poor specificity of phosphate adsorption.
As can be seen from the above discussion, more effective and high safety new serum phosphate lowering agents are needed. Recently, 2′-phosphophloretin (2′-PP) having a Na+ dependent phosphate transporter inhibitory effect is reported (Biochem. Biophys. Res. Commu., 301 (1), 8-12, 2003). It is thought that in vivo activity of the compound is insufficient due to it hydrolyzing by an alkaline phosphatase easily. Therefore, it is hoped that the compound had a potent activity and in vivo efficacy.
This invention aims to offer the newly phosphonate derivatives or the medicinally acceptable salts that have serum phosphate lowering effects.